The US Food and Drug Administration’s (FDA) Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) met this week and voted to against recommending Lipocene’s testosterone <300 ng/dL (TLANDO) replacement therapy, by a count of 13-6.

The FDA is expected to make a decision on the New Drug Application (NDA), which was originally submitted in August 2017, for the product with a Prescription Fee Drug User Act (PDUFA) date of May 8, 2018.

"We continue to believe that efficacy and safety results from numerous clinical studies with TLANDO are consistent with other FDA approved TRT products," Mahesh Patel, PhD, the chairman, president and CEO of Lipocine, said in a statement. "We look forward to continuing to work with the FDA through the remainder of the review process."

The committee voted based on information on efficacy and safety from the results of 3 phase 3 trials—the Dosing Validation (DV) study and the Dosing Flexibility (DF) study, which are ongoing, and the Study of Oral Androgen Replacement (SOAR) trial.

The BRUDAC’s concerns dated back to the Lipocene’s first NDA for the product in 2015, which resulted in a rise in heart rate among patients that received the therapy in adjunct with androgel. Additionally, there was a reported decline in high-density lipoprotein cholesterol in almost 50% of the therapy arm.

Adverse events (AEs) occurred in SOAR at a comparative rate with androgel. AEs occurring at a rate higher than 5% were upper respiratory infection (5.2% with TLANDO vs. 5.8% with androgel), and fatigue (2.4% vs. 6.7%).

None of the cardiac AEs that concerned the BRUDAC prior were reported in more than 1% of the therapy arms, and all lacked a “severe” label. HDL cholesterol did show decline in the testosterone replacement arm, but it was deemed not significantly different from the control. Additionally, there were no hepatic, cardiac, or drug related serious AEs reported with either arm in SOAR.

SOAR, a 52-week, multicenter, randomized, open-label, parallel-group, active-controlled trial including 315 males aged 18 to 80 years old. They were randomized 2:1 to either the Lipocene product (n = 210) or androgel 1.62% (n = 105). The testosterone replacement group were administered 225 mg TU (~ 142 mg of T) twice daily, followed by either a titration upward to 300 mg TU twice daily or downward to 150 mg TU twice daily based on data collected at weeks 3 and 7.

After 52 weeks, 87.4% of the testosterone replacement group met the FDA target of ≥75% of subjects within the average 24-hour serum testosterone concentration (Cavg) within normal range (300 ng/dL to 1140 ng/dL). The second FDA target of a lower bound of 95% CI was met by 81.7% of the testosterone replacement group. In total, 85% of subjects reached their final dosing with only 1 titration, and 52% were finalized with a 225 mg twice daily dose.

Both the DV and DF studies are enrolling up to 100 hypogonadal males each, and are designed with an open-label, fixed dose, no titration, and single-treatment plan. Efficacy will be assessed after the dosing period of 24 days.